Polio eradication: Addressing the hurdles on the last mile.

1988, the World Health Assembly committed to eradicate poliomyelitis, a viral disease that can cause permanent paralysis. Today, only type 1 of the three wild poliovirus types remains circulating in limited geographic areas following widespread use of different poliovirus vaccines. While we are close to zero new cases of wild polio, it is a fragile situation, and there are many remaining and new hurdles to overcome. Here, experts discuss how to address them.

Perpetuation of gender discrimination in Pakistani society: results from a scoping review and qualitative study conducted in three provinces of Pakistan.

BACKGROUND: Gender discrimination is any unequal treatment of a person based on their sex. Women and girls are most likely to experience the negative impact of gender discrimination. The aim of this study is to assess the factors that influence gender discrimination in Pakistan, and its impact on women's life. METHODS: A mixed method approach was used in the study in which a systematic review was done in phase one to explore the themes on gender discrimination, and qualitative interviews were conducted in phase two to explore the perception of people regarding gender discrimination. The qualitative interviews (in-depth interviews and focus group discussions) were conducted from married men and women, adolescent boys and girls, Healthcare Professionals (HCPs), Lady Health Visitors (LHVs) and Community Midwives (CMWs). The qualitative interviews were analyzed both manually and electronically through QSR NVivo 10. The triangulation of data from the systematic review and qualitative interviews were done to explore the gender discrimination related issues in Pakistan. RESULTS: The six major themes have emerged from the systematic review and qualitative interviews. It includes (1) Status of a woman in the society (2) Gender inequality in health (3) Gender inequality in education (4) Gender inequality in employment (5) Gender biased social norms and cultural practices and (6) Micro and macro level recommendations. In addition, a woman is often viewed as a sexual object and dependent being who lacks self identity unless being married. Furthermore, women are restricted to household and child rearing responsibilities and are often neglected and forced to suppress self-expression. Likewise, men are viewed as dominant figures in lives of women who usually makes all family decisions. They are considered as financial providers and source of protection. Moreover, women face gender discrimination in many aspects of life including education and access to health care. CONCLUSION: Gender discrimination is deeply rooted in the Pakistani society. To prevent gender discrimination, the entire society, especially women should be educated and gendered sensitized to improve the status of women in Pakistan.

Indigenous and tribal peoples' health (The Lancet-Lowitja Institute Global Collaboration): a population study.

BACKGROUND: International studies of the health of Indigenous and tribal peoples provide important public health insights. Reliable data are required for the development of policy and health services. Previous studies document poorer outcomes for Indigenous peoples compared with benchmark populations, but have been restricted in their coverage of countries or the range of health indicators. Our objective is to describe the health and social status of Indigenous and tribal peoples relative to benchmark populations from a sample of countries. METHODS: Collaborators with expertise in Indigenous health data systems were identified for each country. Data were obtained for population, life expectancy at birth, infant mortality, low and high birthweight, maternal mortality, nutritional status, educational attainment, and economic status. Data sources consisted of governmental data, data from non-governmental organisations such as UNICEF, and other research. Absolute and relative differences were calculated. FINDINGS: Our data (23 countries, 28 populations) provide evidence of poorer health and social outcomes for Indigenous peoples than for non-Indigenous populations. However, this is not uniformly the case, and the size of the rate difference varies. We document poorer outcomes for Indigenous populations for: life expectancy at birth for 16 of 18 populations with a difference greater than 1 year in 15 populations; infant mortality rate for 18 of 19 populations with a rate difference greater than one per 1000 livebirths in 16 populations; maternal mortality in ten populations; low birthweight with the rate difference greater than 2% in three populations; high birthweight with the rate difference greater than 2% in one population; child malnutrition for ten of 16 populations with a difference greater than 10% in five populations; child obesity for eight of 12 populations with a difference greater than 5% in four populations; adult obesity for seven of 13 populations with a difference greater than 10% in four populations; educational attainment for 26 of 27 populations with a difference greater than 1% in 24 populations; and economic status for 15 of 18 populations with a difference greater than 1% in 14 populations. INTERPRETATION: We systematically collated data across a broader sample of countries and indicators than done in previous studies. Taking into account the UN Sustainable Development Goals, we recommend that national governments develop targeted policy responses to Indigenous health, improving access to health services, and Indigenous data within national surveillance systems. FUNDING: The Lowitja Institute.

Diagnostic accuracy of WHO verbal autopsy tool for ascertaining causes of neonatal deaths in the urban setting of Pakistan: a hospital-based prospective study.

BACKGROUND: Globally, clinical certification of the cause of neonatal death is not commonly available in developing countries. Under such circumstances it is imperative to use available WHO verbal autopsy tool to ascertain causes of death for strategic health planning in countries where resources are limited and the burden of neonatal death is high. The study explores the diagnostic accuracy of WHO revised verbal autopsy tool for ascertaining the causes of neonatal deaths against reference standard diagnosis obtained from standardized clinical and supportive hospital data. METHODS: All neonatal deaths were recruited between August 2006 -February 2008 from two tertiary teaching hospitals in Province Sindh, Pakistan. The reference standard cause of death was established by two senior pediatricians within 2 days of occurrence of death using the International Cause of Death coding system. For verbal autopsy, trained female community health worker interviewed mother or care taker of the deceased within 2-6 weeks of death using a modified WHO verbal autopsy tool. Cause of death was assigned by 2 trained pediatricians. The performance was assessed in terms of sensitivity and specificity. RESULTS: Out of 626 neonatal deaths, cause-specific mortality fractions for neonatal deaths were almost similar in both verbal autopsy and reference standard diagnosis. Sensitivity of verbal autopsy was more than 93% for diagnosing prematurity and 83.5% for birth asphyxia. However the verbal autopsy didn't have acceptable accuracy for diagnosing the congenital malformation 57%. The specificity for all five major causes of neonatal deaths was greater than 90%. CONCLUSION: The WHO revised verbal autopsy tool had reasonable validity in determining causes of neonatal deaths. The tool can be used in resource limited community-based settings where neonatal mortality rate is high and death certificates from hospitals are not available.

Opportunities and challenges for financing women's, children's and adolescents' health in the context of climate change.

Women, children and adolescents (WCA), especially in low-income and middle-income countries (LMICs), will bear the worst consequences of climate change during their lifetimes, despite contributing the least to global greenhouse gas emissions. Investing in WCA can address these inequities in climate risk, as well as generating large health, economic, social and environmental gains. However, women's, children's and adolescents' health (WCAH) is currently not mainstreamed in climate policies and financing. There is also a need to consider new and innovative financing arrangements that support WCAH alongside climate goals.We provide an overview of the threats climate change represents for WCA, including the most vulnerable communities, and where health and climate investments should focus. We draw on evidence to explore the opportunities and challenges for health financing, climate finance and co-financing schemes to enhance equity and protect WCAH while supporting climate goals.WCA face threats from the rising burden of ill-health and healthcare demand, coupled with constraints to healthcare provision, impacting access to essential WCAH services and rising out-of-pocket payments for healthcare. Climate change also impacts on the economic context and livelihoods of WCA, increasing the risk of displacement and migration. These impacts require additional resources to support WCAH service delivery, to ensure continuity of care and protect households from the costs of care and enhance resilience. We identify a range of financing solutions, including leveraging climate finance for WCAH, adaptive social protection for health and adaptations to purchasing to promote climate action and support WCAH care needs.

Infections and nutrient deficiencies during infancy predict impaired growth at 5 years: Findings from the MAL-ED study in Pakistan.

Background: Socio-economic, nutritional, and infectious factors have been associated with impaired infant growth, but how the presence of these factors during infancy affects growth around 5 years is not well understood. Methods: This secondary analysis of the MAL-ED cohort included 277 children from Pakistan for whom socio-demographic, breastfeeding, complementary foods, illness, nutritional biomarkers, stool pathogens and environmental enteropathy indicators between 0 and 11 months were recorded. We used linear regression models to analyze associations of these indicators with height-for-age (HAZ), weight-for-age (WAZ) and weight-for-height (WLZ) at 54-66 months (~5 years), and Poisson regression with robust standard errors to estimate risk ratios for stunting and underweight ~5 years, controlling for gender, first available weight, and income. Results: Among the 237 infants followed longitudinally and evaluated at about 5 years of age, exclusive breastfeeding was short (median = 14 days). Complementary feeding started before 6 months with rice, bread, noodles, or sugary foods. Roots, dairy products, fruits/vegetables, and animal-source foods were provided later than recommended (9-12 months). Anemia (70.9%), deficiencies in iron (22.0%), zinc (80.0%), vitamin A (53.4%) and iodine (13.3%) were common. Most infants (>90%) presented with diarrhea and respiratory infections in their first year. At ~5 years, low WAZ (mean-1.91 ± 0.06) and LAZ (-2.11 ± 0.06) resulted in high prevalence of stunting (55.5%) and underweight (44.4%) but a relatively low rate of wasting (5.5%). While 3.4% had concurrent stunting and wasting ~5 years, 37.8% of children had coexisting stunting and underweight. A higher income and receiving formula or dairy products during infancy were associated with a higher LAZ ~5 years, but infant's history of hospitalizations and more respiratory infections were associated with lower LAZ and higher risk of stunting ~5 years. Infants' intake of commercial baby foods and higher serum-transferrin receptors were associated with higher WAZ and lower risk of underweight ~5 years. Presence of Campylobacter and fecal neopterin >6.8 nmol/L in the first year were associated with increased risk of underweight ~5 years. Conclusion: Growth indicators ~5 years were associated with poverty, inappropriate complementary feeding, and infections during the first year of life, which supports the early start of public health interventions for preventing growth delay ~5 years.

Routine antibiotics for infants less than 6 months of age with growth failure/faltering: a systematic review.

OBJECTIVE: This systematic review commissioned by WHO aimed to synthesise evidence from current literature on the effects of systematically given, routine use of antibiotics for infants under 6 months of age with growth failure/faltering. SETTINGS: Low-income and middle-income countries. PARTICIPANTS: The study population was infants less than 6 months of age with growth failure/faltering. INTERVENTION: The intervention group was infants who received no antibiotics or antibiotics other than those recommended in 2013 guidelines by WHO to treat childhood severe acute malnutrition. The comparison group was infants who received antibiotics according to the aforementioned guidelines. PRIMARY AND SECONDARY OUTCOMES: The primary outcome was all-cause mortality, and secondary outcomes: clinical deterioration, antimicrobial resistance, recovery from comorbidity, adverse events, markers of intestinal inflammation, markers of systemic inflammation, hospital-acquired infections and non-response. The Grading of Recommendations Assessment, Development and Evaluation approach was considered to report the overall evidence quality for an outcome. RESULTS: We screened 5137 titles and abstracts and reviewed the full text of 157 studies. None of the studies from the literature search qualified to answer the question for this systematic review. CONCLUSIONS: There is a paucity of evidence on the routine use of antibiotics for the treatment of malnutrition in infants less than 6 months of age. Future studies with adequate sample sizes are needed to assess the potential risks and benefits of antibiotics in malnourished infants under 6 months of age. PROSPERO REGISTRATION NUMBER: CRD42021277073.

Effect of multiple micronutrient supplementation on pregnancy and infant outcomes: a systematic review.

Supplementation with multiple micronutrients (MM) during pregnancy may result in improved pregnancy and infant outcomes. We conducted meta-analyses of randomised controlled trials that evaluated the effects of prenatal supplementation with MM (defined as containing at least five micronutrients and typically included iron or iron and folic acid). The outcomes of interest were low birthweight (<2500 g), birthweight, small-for-gestational age (SGA), gestational age, preterm birth (<37 weeks' gestation), stillbirth and neonatal death, maternal morbidity and mortality. We identified eligible studies through PubMed and EMBASE database searches. Meta-analyses were performed by pooling results for outcomes that were reported from more than one trial and sub-analyses were conducted to evaluate the effect of timing of intervention and amount of iron. We included published results from 16 trials in this review. Compared with control supplementation that was usually iron plus folic acid in most studies, MM supplementation resulted in a significant reduction in the incidence of low birthweight [pooled risk ratio (RR) 0.86; 95% confidence interval (CI) 0.81, 0.91] and SGA (pooled RR 0.83 [95% CI 0.73, 0.95]) and an increase in mean birthweight (weighted mean difference (WMD) 52.6 g [95% CI 43.2 g, 62.0 g]). There was no significant difference in the overall risk of preterm birth, stillbirth, and maternal or neonatal mortality, but we found an increased risk of neonatal death for the MM group compared with iron-folate in the subgroup of five trials that began the intervention after the first trimester (RR 1.38 [95% CI 1.05, 1.81]). None of the studies evaluated maternal morbidity. Compared with iron plus folic acid supplementation alone, prenatal maternal supplementation with MM resulted in a reduction in the incidence of low birthweight and SGA but increased risk of neonatal death in the subgroup of studies that began the intervention after the first trimester.

Indirect effects of COVID-19 on child and adolescent mental health: an overview of systematic reviews.

INTRODUCTION: To control the spread of COVID-19, mitigation strategies have been implemented globally, which may have unintended harmful effects on child and adolescent mental health. This study aims to synthesise the indirect mental health impacts on children and adolescents globally due to COVID-19 mitigation strategies. METHODS: We included relevant reviews from MEDLINE, Embase, PsycINFO, LILACS, CINAHL, The Cochrane Library and Web of Science until January 2022 that examined the impact of COVID-19-related lockdown and stay-at-home measures on the mental health of children and adolescents. Data extraction and quality assessments were completed independently and in duplicate by BC and LH. A Measurement Tool to Assess Systematic Reviews-2 was used to assess the methodological quality. RESULTS: Eighteen systematic reviews, comprising 366 primary studies, found a pooled prevalence of 32% for depression (95% CI: 27 to 38, n=161 673) and 32% for anxiety (95% CI: 27 to 37, n=143 928) in children and adolescents globally following COVID-19 mitigation measures. Subgroup analyses also uncovered important differences for both depression and anxiety by World Health Organization regions with few studies from Africa and relative high burden of anxiety and depression in the Eastern Mediterranean region. CONCLUSIONS: Our findings reveal a high prevalence of depression and anxiety in children and adolescents during the COVID-19 pandemic, globally, compared with prepandemic estimates. These findings highlight the urgency for governments and policymakers to strengthen mental health systems in the COVID-19 recovery, especially in low-and middle-income countries where compounding psychological stress, access and affordability of care and discrepant reporting of mental health in this population remains a challenge. We also provide insight into how to alter mitigation strategies to reduce the unintended negative consequences for the health and well-being of children and adolescents in future pandemics. PROSPERO REGISTRATION NUMBER: CRD42022309348.

Protocol for a systematic review on routine use of antibiotics for infants less than 6 months of age with growth failure/faltering.

INTRODUCTION: Antibiotics have been used as an adjunct in treating children with severe acute malnutrition 6-59 months of age; however, the data for infants less than 6 months are scarce. The WHO recently started guideline development for preventing and treating wasting, including growth failure/faltering in infants less than 6 months. This systematic review commissioned by WHO aims to synthesise evidence from current literature on the effectiveness of antibiotics for infants less than 6 months of age with growth failure/faltering. METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis for studies that assessed the effect of antibiotics in the treatment of infants with growth faltering. We will search multiple electronic databases. We will include randomised control trials and non-randomised studies with a control arm. The study population is infants less than 6 months of age with growth failure. The intervention group will be infants who received no antibiotics or antibiotics other than recommended in 2013 guidelines by WHO to treat severe acute malnutrition in children. The comparison group will be infants who received antibiotics according to the 2013 guideline by WHO. We will consider the following outcomes: mortality, clinical deterioration, antimicrobial resistance, recovery from comorbidity, adverse events, markers of intestinal inflammation, markers of systemic inflammation, hospital-acquired infections, non-response. We will use the meta-analysis to pool the studies where applicable. We will use the Grading of Recommendations Assessment, Development, and Evaluation approach to reporting the overall evidence quality for an outcome. ETHICS AND DISSEMINATION: This is a systematic review and will not involve contact with a human subject. The findings of this review will be published in a peer-review journal and will guide the WHO's recommendation for the use of antibiotics in infants less than 6 months of age with growth failure. PROSPERO REGISTRATION NUMBER: CRD42021277073.

The Effect of Consumption of Animal Milk Compared to Infant Formula for Non-Breastfed/Mixed-Fed Infants 6-11 Months of Age: A Systematic Review and Meta-Analysis.

Many infants do not receive breastmilk for the recommended 2-year duration. Instead, alternative milk beverages are often used, including infant formula and raw animal milk products. The purpose of this systematic review was to summarize the effect of animal milk consumption, compared to infant formula, on health outcomes in non-breastfed or mixed-fed infants aged 6-11 months. We searched multiple databases and followed Cochrane guidelines for conducting the review. The primary outcomes were anemia, gastrointestinal blood loss, weight-for-age, length-for-age, and weight-for-length. Nine studies were included: four randomized controlled trials (RCT) and five cohort studies. All studies, except one, were conducted in high income countries. There was a low certainty of evidence that cow's milk increased the risk of anemia compared to formula milk (Cohort studies RR: 2.26, 95% CI: 1.15, 4.43, RCTs: RR: 4.03, 95% CI: 1.68, 9.65) and gastrointestinal blood loss (Cohort study RR: 1.52, 95% CI: 0.73, 3.16, RCTs: RR: 3.14, 95% CI: 0.98, 10.04). Additionally, there was low certainty evidence that animal milk consumption may not have a differential effect on weight and length-for-age compared to formula milk. Overall, the evidence was of low certainty and no solid conclusions can be drawn from this data. Further studies are needed from low- and middle-income countries to assess optimal milk type in non-breastfed infants aged 6-11 months.

Optimal iron content in ready-to-use therapeutic foods for the treatment of severe acute malnutrition in the community settings: a protocol for the systematic review and meta-analysis.

INTRODUCTION: The current standard of care for children with severe acute malnutrition (SAM) involves using ready-to-use therapeutic food (RUTF) to promote growth; however, the precise formulation to achieve optimal recovery remains unclear. Emerging research suggests that alternative RUTF formulations may be more effective in correcting SAM-related complications such as anaemia and iron deficiency. This systematic review commissioned by the WHO aims to synthesise the most recent research on the iron content in RUTF and related products in the community-based treatment of uncomplicated severe malnutrition in children aged 6 months and older. METHODS AND ANALYSIS: We will search multiple electronic databases. We will include randomised controlled trials and non-randomised studies with a control arm. The intervention group will be infants who received RUTF treatments other than the current recommended guidelines set forth by the WHO. The comparison group is children receiving RUTF containing iron at the current WHO-recommended level of 1.9 mg/100 kcal (10-14 mg/100 g). The primary outcomes of interest include blood haemoglobin concentration, any anaemia, severe anaemia, iron-deficiency anaemia, recovery from SAM and any adverse outcomes. We will use meta-analysis to pool findings if sufficient homogeneity exists among included studies. The risk of bias in studies will be evaluated using the Cochrane risk of bias-2. We will use the Grading of Recommendations Assessment, Development, and Evaluation(GRADE) approach to examine the overall certainty of evidence. ETHICS AND DISSEMINATION: This is a systematic review and will not involve direct contact with human subjects. The findings of this review will be published in a peer-reviewed journal and will guide the WHO's recommendation on the optimal iron content in RUTFs for the treatment of SAM in children aged 6-59 months.

Increased vs. Standard Dose of Iron in Ready-to-Use Therapeutic Foods for the Treatment of Severe Acute Malnutrition in a Community Setting: A Systematic Review and Meta-Analysis.

The optimal dose of iron in ready-to-use therapeutic foods (RUTF) used to treat uncomplicated severe acute malnutrition (SAM) in community settings is not well established. The objective of this systematic review was to assess if an increased iron dose in RUTF, compared with the standard iron dose in the World Health Organization (WHO)-recommended peanut-based RUTF, improved outcomes in children aged six months or older. We searched multiple electronic databases and only included randomized controlled trials. We pooled the data in a meta-analysis to obtain relative risk (RR) and reported it with a 95% confidence interval (CI). Three studies, one each from Zambia, the Democratic Republic of Congo, and Malawi, were included. In all studies, the RUTF used in the intervention group was milk-free soya-maize-sorghum-based RUTF. The pooled results showed that, compared to the control group, a high iron content in RUTF may lead to increase in hemoglobin concentration (mean difference 0.33 g/dL, 95% CI: 0.02, 0.64, two studies, certainty of evidence: low) and a decrease in any anemia (RR 0.66, 95% CI: 0.48, 0.91, two studies, certainty of evidence: low), but also decrease recovery rates (RR 0.91, 95% CI: 0.84, 0.99, three studies, certainty of evidence: low) and increase mortality (RR 1.30, 95% CI: 0.87, 1.95, three studies, certainty of evidence: moderate). However, the CIs were imprecise for the latter outcome. Future studies with large sample sizes are needed to confirm the beneficial versus harmful effects of high iron content in RUTF in treating uncomplicated SAM in children aged 6-59 months in community settings.

Opportunities and challenges to non-communicable disease (NCD) research and training in Pakistan: a qualitative study from Pakistan.

INTRODUCTION: Most of the global non-communicable disease (NCD)-related death burden is borne by low and middle-income countries (LMICs). In LMICs like Pakistan, however, a major gap in responding to NCDs is a lack of high-quality research leading to policy development and implementation of NCDs. To assess institutional opportunities and constraints to NCD research and training we conducted a situational analysis for NCD research and training at Aga Khan University Pakistan. METHODS: We conducted a descriptive exploratory study using grounded theory as a qualitative approach: semistructured interviews of 16 NCD stakeholders (three excluded) and two focus group discussions with postgraduate and undergraduate trainees were conducted. A simple thematic analysis was done where themes were identified, and then recurring ideas were critically placed in their specific themes and refined based on the consensus of the investigators. RESULTS: The major themes derived were priority research areas in NCDs; methods to improve NCD research integration; barriers to NCD research in LMICs like Pakistan; design of NCD research programme and career paths; and NCD prevention at mass level, policy and link to the government. In general, participants opined that while there was an appetite for NCD research and training, but few high-quality research training programmes in NCDs existed, such programmes needed to be established. The ideal NCD research and training programmes would have in-built protected time, career guidance and dedicated mentorship. Most participants identified cardiovascular diseases as a priority thematic area and health information technology and data science as key methodological approaches to be introduced into research training. CONCLUSION: We conclude from this qualitative study on NCD research and training that high-quality research training programmes for NCDs are rare. Such programmes need to be established with in-built protected time, career guidance and mentorship for the trainees to improve their research capacity in Pakistan.

Characteristics and birth outcomes of pregnant adolescents compared to older women: An analysis of individual level data from 140,000 mothers from 20 RCTs.

BACKGROUND: Adolescence is a critical period of maturation when nutrient needs are high, especially among adolescents entering pregnancy. Using individual-level data from 140,000 participants, we examined socioeconomic, nutrition, and pregnancy and birth outcomes for adolescent mothers (10-19 years) compared to older mothers in low and middle-income countries. METHODS: This study was conducted between March 16, 2018 and May 25, 2021. Data were obtained from 20 randomised controlled trials of micronutrient supplementation in pregnancy. Stratified analyses were conducted by age (10-14 years, 15-17 years, 18-19 years, 20-29 years, 30-39 years, 40+ years) and geographical region (Africa, Asia). Crude and confounder-adjusted means, prevalence and relative risks of pregnancy, nutrition and birth outcomes were estimated using multivariable linear and log-binomial regression models with 95% confidence intervals. FINDINGS: Adolescent mothers comprised 31.6% of our data. Preterm birth, small-for-gestational age (SGA), low birthweight (LBW) and newborn mortality followed a U-shaped trend in which prevalence was highest among the youngest mothers (10-14 years) and then reduced gradually, but increased again for older mothers (40+ years). When compared to mothers aged 20-29 years, there was a 23% increased risk of preterm birth, a 60% increased risk of perinatal mortality, a 63% increased risk of neonatal mortality, a 28% increased risk of LBW, and a 22% increased risk of SGA among mothers 10-14 years. Mothers 40+ years experienced a 22% increased risk of preterm birth and a 103% increased risk of stillbirth when compared to the 20-29 year group. INTERPRETATION: The youngest and oldest mothers suffer most from adverse pregnancy and birth outcomes. Policy and programming agendas should consider both biological and socioeconomic/environmental factors when targeting these populations. FUNDING: Bill and Melinda Gates Foundation (Grant No: OP1137750).

Screening and triage of intrauterine growth restriction (IUGR) in general population and high risk pregnancies: a systematic review with a focus on reduction of IUGR related stillbirths.

BACKGROUND: There is a strong association between stillbirth and fetal growth restriction. Early detection and management of IUGR can lead to reduce related morbidity and mortality. In this paper we have reviewed effectiveness of fetal movement monitoring and Doppler velocimetry for the detection and surveillance of high risk pregnancies and the effect of this on prevention of stillbirths. We have also reviewed effect of maternal body mass index (BMI) screening, symphysial-fundal height measurement and targeted ultrasound in detection and triage of IUGR in the community. METHODS: We systematically reviewed all published literature to identify studies related to our interventions. We searched PubMed, Cochrane Library, and all World Health Organization Regional Databases and included publications in any language. Quality of available evidence was assessed using GRADE criteria. Recommendations were made for the Lives Saved Tool (LiST) based on rules developed by the Child Health Epidemiology Group. Given the paucity of evidence related to the effect of detection and management of IUGR on stillbirths, we undertook Delphi based evaluation from experts in the field. RESULTS: There was insufficient evidence to recommend against or in favor of routine use of fetal movement monitoring for fetal well being. (1) Detection and triage of IUGR with the help of (1a) maternal BMI screening, (1b) symphysial-fundal height measurement and (1c) targeted ultrasound can be an effective method of reducing IUGR related perinatal morbidity and mortality. Pooled results from sixteen studies shows that Doppler velocimetry of umbilical and fetal arteries in 'high risk' pregnancies, coupled with the appropriate intervention, can reduce perinatal mortality by 29 % [RR 0.71, 95 % CI 0.52-0.98]. Pooled results for impact on stillbirth showed a reduction of 35 % [RR 0.65, 95 % CI 0.41-1.04]; however, the results did not reach the conventional limits of statistical significance. This intervention could be potentially recommended for high income settings or middle income countries with improving rates and standards of facility based care. Based on the Delphi, a combination of screening with maternal BMI, Symphysis fundal height and targeted ultrasound followed by the appropriate management could potentially reduce antepartum and intrapartum stillbirth by 20% respectively. This estimate is presently being recommended for inclusion in the LiST. CONCLUSION: There is insufficient evidence to recommend in favor or against fetal movement counting for routine use for testing fetal well being. Doppler velocimetry of umbilical and fetal arteries and appropriate intervention is associated with 29 % (95 % CI 2% to 48 %) reduction in perinatal mortality. Expert opinion suggests that detection and management of IUGR with the help of maternal BMI, symphysial-fundal height measurement and targeted ultrasound could be effective in reducing IUGR related stillbirths by 20%.

Effect of consumption of animal milk compared to infant formula for non-breastfed/mixed-fed infants 6-11 months of age: a systematic review (protocol).

INTRODUCTION: Prevalence rates of breastfeeding remain low even though the World Health Organization (WHO) and the American Academy of Pediatrics recommend exclusive breast feeding for the first 6 months of life in combination with appropriate complementary feeding beyond six 6 months of age. There have been several studies that address the implication of drinking animal milk and/or infant formula on children's health and development when breast feeding is not offered during the first year of life. Vast improvements have been made in infant formula design, which may increase its benefits compared with animal's milk. The objective of this review is therefore to synthesise the most recent evidence on the effects of the consumption of animal milk compared with infant formula in non-breastfed or mixed breastfed infants aged 6-11 months. METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis of studies that assessed the effect of animal milk compared with formula or mixed-fed (breastmilk and formula) on infants aged 6-11 months. The primary outcomes of interest include anaemia, gastrointestinal blood loss, weight for age, height for age and weight for height. We will include randomised and non-randomised studies with a control group. We will use the Cochrane risk of bias tools to assess the risk of bias. We will use meta-analysis to pool findings if the identified studies are conceptually homogenous and data are available from more than one study. We will assess the overall quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. ETHICS AND DISSEMINATION: This is a systematic review, so no patients will be directly involved in the design or development of this study. The findings from this systematic review will be disseminated to relevant patient populations and caregivers and will guide the WHO's recommendations on formula consumption versus animal milk in infants aged 6-11 months. TRIAL REGISTRATION NUMBER: CRD42020210925.

Impact of pulse oximetry on hospital referral acceptance in children under 5 with severe pneumonia in rural Pakistan (district Jamshoro): protocol for a cluster randomised trial.

BACKGROUND: Pneumonia is a leading cause of death among children under 5 specifically in South Asia and sub-Saharan Africa. Hypoxaemia is a life-threatening complication among children under 5 with pneumonia. Hypoxaemia increases risk of mortality by 4.3 times in children with pneumonia than those without hypoxaemia. Prevalence of hypoxaemia varies with geography, altitude and severity (9%-39% Asia, 3%-10% African countries). In this protocol paper, we describe research methods for assessing impact of Lady Health Workers (LHWs) identifying hypoxaemia in children with signs of pneumonia during household visits on acceptance of hospital referral in district Jamshoro, Sindh. METHODS AND ANALYSIS: A cluster randomised controlled trial using pulse oximetry as intervention for children with severe pneumonia will be conducted in community settings. Children aged 0-59 months with signs of severe pneumonia will be recruited by LHWs during routine visits in both intervention and control arms after consent. Severe pneumonia will be defined as fast breathing and/or chest in-drawing, and, one or more danger sign and/or hypoxaemia (Sa02 <92%) in PO (intervention) group and fast breathing and/or chest in-drawing and one or more danger sign in clinical signs (control) group. Recruits in both groups will receive a stat dose of oral amoxicillin and referral to designated tertiary health facility. Analysis of variance will be used to compare baseline referral acceptance in both groups with that at end of study. ETHICS AND DISSEMINATION: Ethical approval was granted by the Ethics Review Committee of the Aga Khan University (4722-Ped-ERC-17), Karachi. Study results will be shared with relevant government and non-governmental organisations, presented at national and international research conferences and published in international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT03588377.

Global report on preterm birth and stillbirth (3 of 7): evidence for effectiveness of interventions.

INTRODUCTION: Interventions directed toward mothers before and during pregnancy and childbirth may help reduce preterm births and stillbirths. Survival of preterm newborns may also be improved with interventions given during these times or soon after birth. This comprehensive review assesses existing interventions for low- and middle-income countries (LMICs). METHODS: Approximately 2,000 intervention studies were systematically evaluated through December 31, 2008. They addressed preterm birth or low birth weight; stillbirth or perinatal mortality; and management of preterm newborns. Out of 82 identified interventions, 49 were relevant to LMICs and had reasonable amounts of evidence, and therefore selected for in-depth reviews. Each was classified and assessed by the quality of available evidence and its potential to treat or prevent preterm birth and stillbirth. Impacts on other maternal, fetal, newborn or child health outcomes were also considered. Assessments were based on an adaptation of the Grades of Recommendation Assessment, Development and Evaluation criteria. RESULTS: Most interventions require additional research to improve the quality of evidence. Others had little evidence of benefit and should be discontinued. The following are supported by moderate- to high-quality evidence and strongly recommended for LMICs: Two interventions prevent preterm births--smoking cessation and progesterone. Eight interventions prevent stillbirths--balanced protein energy supplementation, screening and treatment of syphilis, intermittant presumptive treatment for malaria during pregnancy, insecticide-treated mosquito nets, birth preparedness, emergency obstetric care, cesarean section for breech presentation, and elective induction for post-term delivery. Eleven interventions improve survival of preterm newborns--prophylactic steroids in preterm labor, antibiotics for PROM, vitamin K supplementation at delivery, case management of neonatal sepsis and pneumonia, delayed cord clamping, room air (vs. 100% oxygen) for resuscitation, hospital-based kangaroo mother care, early breastfeeding, thermal care, and surfactant therapy and application of continued distending pressure to the lungs for respiratory distress syndrome CONCLUSION: The research paradigm for discovery science and intervention development must be balanced to address prevention as well as improve morbidity and mortality in all settings. This review also reveals significant gaps in current knowledge of interventions spanning the continuum of maternal and fetal outcomes, and the critical need to generate further high-quality evidence for promising interventions.